Lymphocyte apoptosis and thrombocytopenia in spleen during classical swine fever: role of macrophages and cytokines.

Thirty-two Large White x Landrace pigs, 4 months old, were inoculated with the classical swine fever (CSF) or hog cholera virus strain "Alfort" in order to identify the mechanism responsible for the lymphopenia and thrombocytopenia observed in the spleen during the experimental induction of disease, by immunohistochemical and ultrastructural techniques. Results showed a progressive depletion of splenic lymphoid structures and evidence of platelet aggregation processes. Lymphoid depletion was due to lymphocyte apoptosis, which could not be ascribed to the direct action of the virus on these cells; direct virus action could play only a secondary role in the death of these cells. Absence of severe tissue and endothelial damage, together with moderate procoagulant cytokine levels in the serum, suggest that these pathologies can be ruled out as the cause of platelet aggregation and thrombocytopenia in CSF. Monocyte/macrophages were the main target cells for the CSF virus, and they exhibited phagocytic and secretory activation leading to the synthesis and release of tumor necrosis factor alpha, which proved to be the chief mediator, followed by IL-6, IL-1alpha, and C1q complement component. In view of their characteristics, TNF-alpha and, to a lesser extent, IL-1alpha and IL-6 appear to be the major cytokines involved in the pathogenesis of lymphocytopenia and thrombocytopenia; a clear spatial and temporal relationship was observed between these two phenomena.